UK scientists have discovered a way of fooling bone marrow into making extra adult stem cells, opening the door to new treatments that stimulate the body to produce its own repair kit of stem cells to mend damaged heart tissue or even a broken bone.

The study was the work of researchers based at the Leukocyte Biology Section of the National Heart and Lung Institute at Imperial College in London, and is published in the 9 January issue of Cell Stem Cell.

An injury to any part of the body causes bone marrow to mobilize different types of stem cell to help with tissue regeneration and repair. This study shows it may be possible to boost this natural process and speed up repair, using drugs that put bone marrow into a state of “red alert”.

For the study, researchers used healthy mice and gave them drugs that tricked their bone marrow into releasing two types of adult stem cells: endothelial progenitor cells that make new blood vessels, and mesenchymal stem cells, that can turn bone into cartilage and can also suppress the immune system.

The study is thought to be the first to selectively mobilize these two types of stem cell from bone marrow. Other researchers have only been able to mobilize stem cells that make new blood vessels, the so-called haematopoietic cells: a technique that is already used in bone marrow transplants to boost blood levels of haematopoietic cells in the donor.

The researchers used different drugs to mobilize the two types of stem cells. They hope their findings will help to develop new therapies to repair and regenerate damaged tissue: for example in heart patients and sports injuries. Another application could be to stimulate bone marrow to generate more immune suppressing stem cells as a way to treat autoimmune disease such as rheumatoid arthritis where the body’s own immune system attacks itself.

For the study, corresponding author Dr Sara Rankin and colleagues treated healthy mice with two growth factors that occur naturally in bone marrow, VEGF and G-CSF, and then gave them a new drug called Mozobil.

Compared with mice that had no treatment, the bone marrow of the mice that were given VEGF followed by Mozobil released about 100 times more endothelial and mesenchymal stem cells into the bloodstream. The bone marrow of mice treated with G-CSF and Mozobil released more haematopoietic stem cells; this is the treatment that is already used in bone marrow transplants.

As Rankin explained:

“The body repairs itself all the time. We know that the skin heals over when we cut ourselves and, similarly, inside the body there are stem cells patrolling around and carrying out repair where it’s needed.”

“However, when the damage is severe, there are limits to what the body can do of its own accord,” she added.

By releasing the extra stem cells, the researchers hope their method will help the body to accelerate the repair process.

“Further down the line, our work could lead to new treatments to fight various diseases and injuries which work by mobilising a person’s own stem cells from within,” said Rankin.

Rankin and colleagues now want to find out if releasing repair stem cells into the bloodstream results in faster and better repair of damaged heart tissue in mice that have had a heart attack.

If they get the results they hope to get, clinical trials of new drugs using this method could be under way within the next ten years.

Another avenue they want to investigate is the extent to which ageing or disease affects the ability of bone marrow to produce different kinds of adult stem cells. Perhaps there is a way to boost this process to help older people fight disease and injury.

The study was funded by the British Heart Foundation, the Wellcome Trust, a European Community INNOCHEM grant and the Brazilian National Council of Technological and Scientific Development (CNPq).

“Differential Mobilization of Subsets of Progenitor Cells from the Bone Marrow.”
Simon C. Pitchford, Rebecca C. Furze, Carla P. Jones, Antje M. Wengner, Sara M. Rankin
Cell Stem Cell 9 January 2009 (Vol. 4, Issue 1, pp. 62-72)
doi:10.1016/j.stem.2008.10.017

Click here for Abstract.

Sources: Cell Stem Cell, Wellcome Trust.

Written by: Catharine Paddock, PhD